A model is proposed for the regulation of energy balance by the level of fat in food restricted diets. The objective is to characterize this model and to delineate the mechanisms by which it operates. In a state of energy balance, energy intake = energy expenditure (EE) and the proportion of fat:carbohydrate in the diet equals that in the fuel mix oxidized by the body. The typical obese person eating a high fat diet has large reserves of body fat, insulin resistance and high levels of free fatty acids (FFA). These contribute to a high level of fat oxidation. When such an obese individual limits food intake of a high fat diet, body fat must be mobilized to provide energy, but fat oxidation must remain high to balance the high proportion of fat in the diet. When obese individuals limit energy intake but also change to a high carbohydrate (CHO) diet, body fat will be mobilized to meet energy needs, but now the proportion of (CHO) in the fuel mix oxidized must be increased to match that of the diet before a new energy balance can be reached. Our model suggests that this requirement necessitates reductions in body fat and insulin resistance so that plasma FFA levels are reduced. Fat oxidation is largely determined by FFA levels. Therefore, lower FFA levels would result in a reduction in fat oxidation and consequently an increase in CHO oxidation. When the proportion of CHO oxidized increases to the proportion in the diet, energy balance is reestablished. According to this model, the level of fat in the food restricted diet determines how much body fat is lost when food intake is restricted. This proposal will determine if individuals who are more susceptible to weight gain with high fat diets are also more resistant to weight loss when food restricted to high CHO diets and if high fat diets alter energy balance differently in females versus males. The mechanisms by which high fat diets might determine energy balance will be studied: insulin resistance, reduced response to SNS stimulation and site specific alterations in the activity of lipoprotein lipase. The long range goal of this work is to improve methods to treat and prevent obesity and thereby reduce the health risks with which obesity is associated.